The present invention relates to pharmaceutical compounds, compositions and methods of their use. Such compounds are pharmacologically useful in the treatment of cardiac arrhythmias in mammals. More specifically, the compounds of the present invention are orally active Class III antiarrhythmic agents which, by effectively prolonging repolarization of a cardiac cell action potential, can be used effectively to treat certain cardiac arrhythmias. At the present time, there is a need in the area of cardiology therapy for such an agent.
Antiarrhythmic drugs have been grouped together according to the pattern of electrophysiological effects that they produce and/or their presumed mechanisms of action. Thus, Class I antiarrhythmic agents are characterized by being sodium channel blockers, Class II antiarrhythmic agents are beta-adrenergic receptor blockers, Class III antiarrhythmic agents prolong repolarization and Class IV antiarrhythmic agents are calcium channel blockers.
Currently, there are very few Class III antiarrhythmic agents available for therapeutic use. Among the available agents is bretylium. Bretylium's usefulness is limited however, and currently its therapeutic use is reserved for life-threatening ventricular arrhythmias that are refractory to therapy. Thus, bretylium's use is generally confined to intensive care units. Sotalol is another known compound being developed as a Class III antiarrhythmic.
Accordingly, it is an object of this invention to provide Class III antiarrhythmic pharmaceutical agents of broader therapeutic use than existing Class III antiarrhythmic agents. There is a need in the area of cardiovascular therapeutics for an agent which has broader clinical usefulness. Various compounds have been disclosed as being useful Class III antiarrhythmics. See for example EP 379,441and EP 379,440. The compounds of the present invention meet the need for an agent which has broad clinical usefulness by providing for orally active therapeutic agents for the treatment of cardiac arrhythmias.